Pharmaceutical active agents can be administered orally or as an injectable. However, conventional oral and injectable formulations are typically short-acting and often require frequent dosing to maintain a therapeutically effective concentration in the blood stream or at sites where treatment is needed. During the past three decades, controlled drug delivery technologies have been developed to control the rate and period of drug delivery and target specific areas of the body for treatment. Controlled drug delivery technologies offer a number of advantages such as prolonged and improved efficacy, decreased dosing frequency, reduced peak-valley plasma concentration fluctuations, decreased side effects, site-specific delivery, ease of administration, patient compliance, and cost reduction. Although oral drug delivery is the most frequently used route of drug administration, parenteral drug delivery is a preferred route for rapid action. Drug products are administered by implantation, or by subcutaneous, intramuscular, or intraperitoneal injection.
Sustained release or controlled release pharmaceutical drug products have also been developed, e.g., by microencapsulation such as microspheres, microparticles, or implants. A drug delivery vehicle most often consists of a polymeric matrix from which drug is released by diffusion from the matrix and/or by degradation of the matrix.
The earliest drug delivery systems (for the delivery of therapeutic agents) were based on a synthetic biodegradable polymer, polylactic acid (Yolles et al., Polymer News, 1:9-15 (1970)). Numerous other polymers have been described for use in biodegradable/bioerodible matrices for controlled release of active agents. U.S. Pat. Nos. 4,079,038, 4,093,709, 4,131,648, 4,138,344, 4,180,646, 4,304,767 and 4,946,931 describe various types of biodegradable/bioerodible polymers for the controlled delivery of active agents. Although many of these polymers are in the form of semi-solid, however, these semi-solid polymers are often very sticky, and thus the formulations prepared cannot be easily injected.
While the above systems are useful, their manufacture processes are complicated, cumbersome and expensive. In addition, they are often associated with an initial higher release of drug immediately after injection followed by inconsistent drug release kinetics, thus lack of reliability in therapeutic effects in animal studies and human trials.